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The Microbiome-Gut-Brain Axis and Resilience to Developing Anxiety or Depression under Stress.
Episodes of depression and anxiety commonly follow the experience of stress, however not everyone who experiences stress develops a mood disorder. Individuals who are able to experience stress without a negative emotional effect are considered stress resilient. Stress-resilience (and its counterpart stress-susceptibility) are influenced by several psychological and biological factors, including the microbiome-gut-brain axis. Emerging research shows that the gut microbiota can influence mood, and that stress is an important variable in this relationship. Stress alters the gut microbiota and plausibly this could contribute to stress-related changes in mood. Most of the reported research has been conducted using animal models and demonstrates a relationship between gut microbiome and mood. The translational evidence from human clinical studies however is rather limited. In this review we examine the microbiome-gut-brain axis research in relation to stress resilience.
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N-3 PUFA Ameliorates the Gut Microbiota, Bile Acid Profiles, and Neuropsychiatric Behaviours in a Rat Model of Geriatric Depression.
The brain-gut-microbiome (BGM) axis affects host bioinformation. N-3 polyunsaturated fatty acids (PUFAs) alleviate cognitive impairment and depression in older adults. This study investigated altered microbiota-bile acid signalling as a potential mechanism linking fish oil-induced gut changes in microbiota to alleviate psychological symptoms. Sprague Dawley rats were fed a fish oil diet and administered D-galactose combined with chronic unpredictable mild stress (CUMS) to simulate geriatric depression. The cognitive function, psychological symptoms, microbiota compositions, and faecal bile acid profiles of the rats were assessed thereafter. A correlation analysis was conducted to determine whether the fish oil-induced alteration of the rats' microbiota and bile acid profiles affected the rats' behaviour. D-galactose and CUMS resulted in lower concentrations of Firmicutes, significantly altered bile acid profiles, and abnormal neurobehaviours. Fish oil intake alleviated the rats' emotional symptoms and increased the abundance of Bacteroidetes, Prevotellaceae, Marinifilaceae, and Bacteroidesuniformis. It also elevated the concentrations of primary bile acids and taurine-conjugated bile acids in the rats' faeces. The rats' taurine-conjugated bile acid levels were significantly correlated with their behavioural outcomes. In short, fish oil intake may alleviate psychological symptoms by altering the microbial metabolites involved in the BGM axis, especially in the conjugation of bile acids.
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American Academy of Pain Medicine and Integrative Healthcare Symposium.
Featured topics: benzhydrocodone, hydrocodone, and an opioid taper program at the American Academy of Pain Medicine; and disruption of the gut microbiome by drugs plus new approaches to depression at the Integrative Healthcare Symposium.
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Impending Mental Health Issues During Coronavirus Disease 2019 - Time for Personalized Nutrition Based on the Gut Microbiota to Tide Over the Crisis?
Coronavirus disease 2019 (COVID-19) is a major pandemic facing the world today caused by SARS-CoV-2 which has implications on our mental health as well. The uncertain future, fear of job loss, lockdown and negative news all around have taken a heavy toll on the mental health of individuals from across the world. Stress and anxiety can affect the COVID-19 patients even more. Recent study suggests COVID-19 infection may lead to post-traumatic stress disorder (PTSD). Certain prebiotics and probiotics have been shown to have anxiolytic effect through gut microbiota modulation. Incidentally, preliminary report also suggests a differential microbial profile in COVID-19 patients as compared to healthy individuals. Gut microbiota's role in anxiety and depression is well studied. The importance of the "gut-brain" axis has been implicated in overall mental health. It is known that diet, environmental factors and genetics play an important role in shaping gut microbiota. Trials may be initiated to study if personalized diet and supplementation based on individual's gut microbiome profile may improve the general mental well-being of people prone to anxiety during this pandemic. Also, COVID-19 patients may be provided personalized nutritional therapy based on their gut microbiota profile to see if PTSD and anxiety symptoms can be alleviated.
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Depression-associated gut microbes, metabolites and clinical trials.
Depression is one of the most prevalent mental disorders today. Over the past decade, there has been considerable attention given to the field of gut microbiota associated with depression. A substantial body of research indicates a bidirectional communication pathway between gut microbiota and the brain. In this review, we extensively detail the correlation between gut microbiota, including Lactobacillus acidophilus and Bifidobacterium longum, and metabolites such as short-chain fatty acids (SCFAs) and 5-hydroxytryptamine (5-HT) concerning depression. Furthermore, we delve into the potential health benefits of microbiome-targeted therapies, encompassing probiotics, prebiotics, and synbiotics, in alleviating depression. Lastly, we underscore the importance of employing a constraint-based modeling framework in the era of systems medicine to contextualize metabolomic measurements and integrate multi-omics data. This approach can offer valuable insights into the complex metabolic host-microbiota interactions, enabling personalized recommendations for potential biomarkers, novel drugs, and treatments for depression.
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Combined Effects of Three High-Energy Charged Particle Beams Important for Space Flight on Brain, Behavioral and Cognitive Endpoints in B6D2F1 Female and Male Mice.
The radiation environment in deep space includes the galactic cosmic radiation with different proportions of all naturally occurring ions from protons to uranium. Most experimental animal studies for assessing the biological effects of charged particles have involved acute dose delivery for single ions and/or fractionated exposure protocols. Here, we assessed the behavioral and cognitive performance of female and male C57BL/6J × DBA2/J F1 (B6D2F1) mice 2 months following rapidly delivered, sequential irradiation with protons (1 GeV, 60%), 16O (250 MeV/n, 20%), and 28Si (263 MeV/n, 20%) at 0, 25, 50, or 200 cGy at 4-6 months of age. Cortical BDNF, CD68, and MAP-2 levels were analyzed 3 months after irradiation or sham irradiation. During the dark period, male mice irradiated with 50 cGy showed higher activity levels in the home cage than sham-irradiated mice. Mice irradiated with 50 cGy also showed increased depressive behavior in the forced swim test. When cognitive performance was assessed, sham-irradiated mice of both sexes and mice irradiated with 25 cGy showed normal responses to object recognition and novel object exploration. However, object recognition was impaired in female and male mice irradiated with 50 or 200 cGy. For cortical levels of the neurotrophic factor BDNF and the marker of microglial activation CD68, there were sex × radiation interactions. In females, but not males, there were increased CD68 levels following irradiation. In males, but not females, there were reduced BDNF levels following irradiation. A significant positive correlation between BDNF and CD68 levels was observed, suggesting a role for activated microglia in the alterations in BDNF levels. Finally, sequential beam irradiation impacted the diversity and composition of the gut microbiome. These included dose-dependent impacts and alterations to the relative abundance of several gut genera, such as Butyricicoccus and Lachnospiraceae. Thus, exposure to rapidly delivered sequential proton, 16O ion, and 28Si ion irradiation significantly affects behavioral and cognitive performance, cortical levels of CD68 and BDNF in a sex-dependent fashion, and the gut microbiome.
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Man and the Microbiome: A New Theory of Everything?
The gut microbiome is implicated in the pathophysiology of a wide range of psychological disorders. Preclinical studies have provided us with key insights into the mechanisms by which the microbiome influences bidirectional gut-brain communication. There are many signaling pathways involved, including the hypothalamic-pituitary-adrenal axis, immune modulation, tryptophan and serotonin metabolism, bile acid transformation, microbial production of neuroactive compounds, and regulation of the endocannabinoid system. The complex and widespread influence of the microbiome on many physiological and psychological processes has generated a keen interest in its therapeutic potential for depression, anxiety, autism, and other psychiatric disorders. It has been shown that the microbiome composition of people suffering with such conditions differs significantly from that of healthy controls, and although the area is in its infancy, interventional studies that alter a person's microbiome through the use of probiotics, prebiotics, or dietary change can alleviate psychopathological symptoms.
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The role of gut microbiome in the pathophysiology of PTSD, depression, and anxiety disorders.
Posttraumatic stress disorder (PTSD), depression, and anxiety disorders are prevalent and often overlapping mental health conditions with complex, multifactorial etiologies. Growing evidence implicates the gut microbiome in their pathophysiology through immune modulation, neurotransmitter regulation, and bidirectional gut-brain signaling. Findings remain fragmented and difficult to reconcile due to differences in study populations, clinical contexts, and analytic methods. This structured narrative review synthesizes current evidence on gut microbial alterations in PTSD, depression, and anxiety, while examining methodological sources of heterogeneity. We searched four databases: PubMed, Scopus, Web of Science, and PsycINFO, and identified 64 eligible studies assessing the gut microbiome composition in these disorders. Sample sizes ranged from small, exploratory cohorts (≈20 participants) to large population-based datasets (>1000 participants), with most studies conducted in China. Stool sampling and DNA extraction protocols varied widely, although 16S rRNA gene amplicon sequencing of the V3-V4 region on Illumina platforms predominated. Alpha-diversity results were inconsistent, whereas beta-diversity analyses distinguished cases from controls. Across these disorders, alterations in microbial composition was observed, including enrichment of proinflammatory and depletion of beneficial bacterial taxa. The current findings indicate that that the gut microbiome represents a promising avenue for biomarker discovery and therapeutic innovation.
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The Impact of Starvation on the Microbiome and Gut-Brain Interaction in Anorexia Nervosa.
Interactions between the gut microbiome and the brain are of increasing interest to both researchers and clinicians. Evidence is mounting on the causal role of an altered gut microbiome in inflammatory diseases such as arthritis, inflammatory bowel disease, obesity and diabetes, and psychiatric diseases like anxiety and depression. Mechanisms include altered energy harvest from food, hormonal changes, increased gut permeability, inflammation, immune response, and a direct influence on the brain and behavior. Anorexia nervosa (AN) is the third most common disease in adolescence and exacts a high burden on patients and caregivers. It often becomes chronic and has the highest mortality of all psychiatric diseases. As AN is characterized by nutritional restrictions, weight loss, and severe behavioral symptoms including weight phobia, comorbid anxiety and depression, accompanied by endocrine alterations, increased inflammation, and immune response, exploring the role of the gut microbiome is crucial. Here, we present an overview of the potential mechanisms of interaction between the gut microbiome, the host and particularly the brain in AN and summarize the initial findings of microbiome research on AN. We conclude by identifying future research directions and potential therapeutic approaches, including nutritional interventions, probiotics, prebiotics and food supplements, that could become important additions to current AN therapy.
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Intestinal microbial remodeling and metabolite regulation may be related to the improvement of social avoidance in depressed mice by Modified Xiaoyaosan.
BACKGROUND: Increased intestinal permeability is implicated in the pathogenesis of depression. Modified Xiaoyaosan (MXYS) has demonstrated antidepressant-like effects in chronic social defeat stress (CSDS) mice, particularly in improving social avoidance behavior. However, direct evidence that MXYS improves depressive behavior by regulating intestinal permeability remains lacking. METHODS: Using a CSDS-induced depression mouse model, we investigated the effects of MXYS through an integrated multi-omics approach, combining intestinal histopathology, microbiome, metabolomics, and molecular biology techniques. This strategy allowed systematic assessment of pathological changes, gut microbial composition, metabolite profiles, and protein expression. RESULTS: MXYS treatment significantly alleviated social avoidance behavior in CSDS mice. It upregulated the expression of tight junction proteins in the colon, jejunum, and hippocampus. MXYS also reduced serum permeability markers of lipopolysaccharide (LPS), D-lactate (D-Lac), and diamine oxidase (DAO), as well as concentrations of pro-inflammatory cytokines TNF-α and IL-1β in both intestinal tissues and the hippocampus. Gut microbiota analysis revealed that MXYS notably decreased the relative abundance of Desulfovibrio in the colon, which was associated with modulation of β-alanine metabolism. In the jejunum, MXYS increased the relative abundance of Clostridium sp. mbf VZ-132 and influenced glycerophospholipid metabolism. CONCLUSION: MXYS alleviates social avoidance in CSDS-induced depressed mice is associated with the restoration of intestinal barrier function via gut microbiota-mediated pathways. Specifically, it may reduces colon Desulfovibrio abundance to modulate β-alanine/aspartate metabolism and enhance claudin-1 expression, while increasing jejunal Clostridium sp. mbf VZ-132 to regulate glycerophospholipid metabolism and upregulate occludin expression. These findings suggested that MXYS may improves depression-like behavior through segment-specific microbial and metabolic modulation of intestinal permeability.